Prokineticins are secreted proteins that have roles in several biological functions, including circadian rhythm; angiogenesis; gastric contractility and motility; gastric acid and pepsinogen secretion; pain; and neurogenesis. Prokineticin 1 (PK1) and prokineticin 2 (PK2) induce cellular responses by binding to G-protein coupled receptors termed prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2), resulting in activation of receptor signaling. Normal prokineticin receptor signaling contributes to the development and function of a variety of tissues in humans. If this normal signaling is disrupted, for example, due to disease, unwanted changes can occur at the cellular, tissue and whole organism level. These changes can be manifested in a variety of conditions and diseases associated with improper prokineticin receptor signaling.
To treat conditions associated with improper prokineticin receptor signaling, it is desirable to identify drugs that alter receptor activity to obtain a normal or otherwise optimal amount of signaling. Such drugs can be used, for example, to increase receptor signaling in individuals having conditions associated with insufficient prokineticin receptor activity or to decrease receptor signaling in individuals having conditions associated with excessive prokineticin receptor activity. Therefore, the identification of prokineticin receptor modulating drugs is expected to provide relief to individuals suffering from a variety of conditions attributed, at least in part, to insufficient or excessive prokineticin receptor signaling.
Thus, there exists a need to identify compounds and methods for modulating prokineticin receptor signaling. The invention satisfies this need and provides related advantages as well.